Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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Manganese Superoxide Dismutase (Sod2) and Redox-Control of Signaling Events That Drive Metastasis

Author(s): Nadine Hempel, Pauline M. Carrico, J. Andres Melendez.

Abstract:

Manganese superoxide dismutase (Sod2) has emerged as a key enzyme with a dual role in tumorigenic progression. Early studies were primarily directed at defining the tumor suppressive function of Sod2 based on its low level expression in many tumor types. It is now commonly held that loss of Sod2 expression is likely an early event in tumor progression allowing for further propagation of the tumorigenic phenotype resulting from steady state increases in free radical production. Increases in free radical load have also been linked to defects in mitochondrial function and metastatic disease progression. It was initially believed that Sod2 loss may propagate metastatic disease progression, in reality both epidemiologic and experimental evidence indicate that Sod2 levels increase in many tumor types as they progress from early stage non-invasive disease to late stage metastatic disease. Sod2 overexpression in many instances enhances the metastatic phenotype that is reversed by efficient H2O2 scavenging. This review evaluates the many sequelae associated with increases in Sod2 that impinge on the metastatic phenotype. The ability to use Sod2 to modulate the cellular redox-environment has allowed for the identification of redox-responsive signaling events that drive malignancy, such as invasion, migration and prolonged tumor cell survival. Further studies of these redox-driven events will help in the development of targeted therapeutic strategies to efficiently restrict redox-signaling essential for malignant progression.

Keywords: Superoxide dismutase, metastasis, signal transduction, matrix metalloproteinases, hydrogen peroxide, single nucleotide polymorphisms (SNP), sarcoma, lymph node invasion, p53-mediated, MDA-MB231, MMP-1 gene, epithelial cells, metastatic bladder, intercalating agents, PTEN mutagenesis

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Article Details

VOLUME: 11
ISSUE: 2
Page: [191 - 201]
Pages: 11
DOI: 10.2174/187152011795255911
Price: $58